Melatonin, which is a hormone secreted from pineal gland and serves the function of adjusting biological clock. People can stay awake during the daytime because the secretion of melatonin is suppressed by the exposure to light. On the other hand, the secretion of melatonin will increase during the nighttime and thus people can fall asleep. The secretion of melatonin in the nighttime would be insufficient if one maintains a lifestyle of working at night or irregular shifts, being nervous, and/or using electronics for a long period of time. The insufficient secretion of melatonin will reduce the sleep quality or even cause sleep disturbances (e.g., insomnia) and/or problems (e.g., feeling tired in the daytime, messing up the biological clock, decreasing the immunity), and thus seriously affect the daily life.
Medicines generally used in clinic for treating sleep disturbance include sedative-hypnotic drugs (e.g., benzodiazepine and barbiturate) and antidepressants (e.g., clomipramine and imipramine). However, the afore-mentioned medicines are prone to cause addiction and may have side effects such as hypersomnia, nausea, headache, vomiting, gastrointestinal discomfort, memory impairment, rebound insomnia, unconsciousness, ataxia, dyspnea, and/or somnambulism. Currently, melatonin being extracted from the pineal glands of cows and/or being chemically synthesized is also commercially available, while such melatonin is strictly controlled or forbidden in the countries that have concerns about mad cow disease and/or the uncertain safe dose of melatonin. Therefore, there is necessity and urgency for continuously developing a medicine or method for treating insomnia and/or ameliorating sleep disturbances effectively without causing addictions and side effects.
It was revealed that the expression of melatonin is regulated by genes such as TPH1 gene, DDC gene, AANAT gene and ASMTL gene, wherein an increased expression of TPH1 gene, DDC gene, AANAT gene, and/or ASMTL gene is helpful for increasing the synthesis of melatonin, and promoting the secretion of melatonin, thereby achieves the effects of treating insomnia, ameliorating sleep disturbance, and regulating sleep.
Inventors of the present invention discovered that a compound of the following formula (I) (i.e., hydroxyanigorufone) is effective in increasing the expression of genes such as TPH1 gene, DDC gene, AANAT gene and ASMTL gene, and thus, can be used for increasing the synthesis of melatonin and/or promoting the secretion of melatonin, thereby achieves the effects of treating insomnia, ameliorating sleep disturbances, and regulating sleep. Compound of formula (I) is also effective in treating, preventing or regulating diseases or physiological functions related to the above genes:
